In order to gain a better understanding of the neurobiology of positive feedback on gonadotropin secretion, we are studying the hormonal regulation of neurotransmitter expression in the anteroventral periventricular nucleus of the preoptic region (AVPV) of juvenile female rats. The AVPV is a sexually dimorphic nucleus that plays an essential role in regulating preovulatory surges of luteinizing hormone (LH) and prolactin secretion and contains sexually dimorphic populations of neurotransmitter specific neurons that are regulated differentially by estrogen (E2) and progesterone (P4). Glutamate is an important regulator of GnRH secretion during pubertal development, but its sites of action remain largely unknown. Progress during the last year includes an immunohistochemical examination of presynaptic NMDA (RI) receptor expression in the hypothalamus. These receptors participate in regulating glutamate release and were largely localized to the periventricular zone (inc luding th e AVPV) suggesting they play an important role in regulating secretion of hormones from the anterior pituitary. Moreover, experiments in progress suggest that progesterone, but not estradiol, regulate expression of these presynaptic receptors in the AVPV. In addition, we demonstrated that treatment of ovariectomized juvenile rats with exogenous estradiol caused a significant increase in the ratio of GluR1/GluR2 mRNAs in the AVPV. These findings suggest that estrogen may facilitate Ca2+ influx in the AVPV by inducing the expression of GluR1 and we are currently using calcium imaging to test this hypothesis directly. Moreover, we have adapted this method for the study of primate prefrontal cortex in preparation for experiments that will examine the role of hormones in regulating glutamatergic signaling in the nonhuman primate brain. FUNDING NIH NS26723 PUBLICATIONS Simerly RB. Organization and regulation of sexually dimorphic neuroendocrine pathways. Behav Brain Res 92:195-203,1998. Gu GB, Varoqueaux F, Ibanez MA, Kirigiti MA, Simerly RB. Preferential expression of presynaptic NMDA receptors in the periventricular zone of the hypothalamus. Soc Neurosci Abstr 24:91, 1998 (abstract 41.5).